The ultimate embodiment of an extracorporeal closed-loop blood-glucose control system will be a portable de- vice consisting of three components: a continuous glucose monitor (CGM), a continuous subcutaneous (SC) drug infusion device (e.g. an insulin pump), and a control algorithm. The control algorithm links the other two components by receiving the glucose data stream from the CGM, making a therapeutic decision based on that data stream, and issuing commands to the drug infusion device. We have designed and tested closed-loop control systems that safely and effectively regulate blood-glucose (BG) levels based on either a venous BG data stream (in diabetic pigs and in people with type 1 diabetes) or a CGM data stream (in diabetic pigs). We have further tested our CGM-based closed-loop control system in diabetic pigs using both an insulin-only configuration and a bihormonal (insulin and glucagon) configuration. Based on our positive preclinical results, we hypothesize that our CGM-based closed-loop glucose-control system can provide safe and effective BG control in people with type 1 diabetes. Our objective is to test this hypothesis and optimize our closed-loop system by conducting human trials in the Mallinckrodt Clinical Research Center at the Massachusetts General Hospital on healthy adult volunteers (18 years and older) with type 1 diabetes. We propose to achieve this objective with the following three specific aims: (1) to test the safety and efficacy of our control system (in both the bihormonal and insulin-only configurations) in regulating BG in adults with type 1 diabetes based on interstitial-fluid (ISF) glucose data from a CGM, (2) to repeat the study of Aim 1 using the same control system with the addition of periods of structured exercise in the study protocol, and (3) to conduct 5-day continuous closed-loop in-patient studies using a fully integrated PDA-based portable control system in adults with type 1 diabetes. PUBLIC HEALTH RELEVANCE: Good, consistent management of blood sugar levels in people with type 1 diabetes is essential to prevent or minimize health complications. Our goal is to develop an engineering system that would automatically manage blood sugar in people with type 1 diabetes by developing a computer program that would link a sensing device that automatically and frequently estimates a person's blood sugar with a small pump that automatically delivers insulin to lower blood sugar. If successful, the system will provide good and safe management of blood sugar, and reduce the health complications that may arise with diabetes.